Variant 11-4992236-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021801.5(MMP26):c.780A>G(p.Ile260Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00332 in 1,610,454 control chromosomes in the GnomAD database, including 167 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.018 ( 83 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 84 hom. )

Consequence

MMP26
NM_021801.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.67

Variant links:

Genes affected

MMP26 (HGNC:14249): (matrix metallopeptidase 26) Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. The encoded preproprotein is proteolytically processed to generate the mature enzyme. This enzyme may degrade collagen type IV, fibronectin, fibrinogen, and beta-casein, and activate matrix metalloproteinase-9 by cleavage. The protein differs from most MMP family members in that it lacks a conserved C-terminal protein domain. The encoded protein may promote cell invasion in multiple human cancers. [provided by RefSeq, May 2016]

MMP26 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037540793).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MMP26	NM_021801.5 linkuse as main transcript	c.780A>G	p.Ile260Met	missense_variant	8/8	ENST00000380390.6
MMP26	NM_001384608.1 linkuse as main transcript	c.570A>G	p.Ile190Met	missense_variant	8/8
MMP26	XM_011520219.3 linkuse as main transcript	c.570A>G	p.Ile190Met	missense_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
MMP26	ENST00000380390.6 linkuse as main transcript	c.780A>G	p.Ile260Met	missense_variant	8/8	5	NM_021801.5	P1
MMP26	ENST00000300762.2 linkuse as main transcript	c.570A>G	p.Ile190Met	missense_variant	8/8	1
MMP26	ENST00000690848.1 linkuse as main transcript	c.780A>G	p.Ile260Met	missense_variant	7/7			P1

Frequencies

GnomAD3 genomes

AF:

0.0183

AC:

2782

AN:

151692

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0639

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00684

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000623

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.0139

GnomAD3 exomes

AF:

0.00480

AC:

1172

AN:

244120

Hom.:

AF XY:

0.00330

AC XY:

437

AN XY:

132376

show subpopulations

Gnomad AFR exome

AF:

0.0677

Gnomad AMR exome

AF:

0.00265

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000667

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000165

Gnomad OTH exome

AF:

0.00236

GnomAD4 exome

AF:

0.00175

AC:

2550

AN:

1458644

Hom.:

Cov.:

AF XY:

0.00151

AC XY:

1096

AN XY:

725560

show subpopulations

Gnomad4 AFR exome

AF:

0.0627

Gnomad4 AMR exome

AF:

0.00287

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000693

Gnomad4 OTH exome

AF:

0.00389

GnomAD4 genome

AF:

0.0184

AC:

2793

AN:

151810

Hom.:

Cov.:

AF XY:

0.0181

AC XY:

1339

AN XY:

74164

show subpopulations

Gnomad4 AFR

AF:

0.0640

Gnomad4 AMR

AF:

0.00683

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.0138

Alfa

AF:

0.00326

Hom.:

Bravo

AF:

0.0211

ESP6500AA

AF:

0.0652

AC:

287

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00588

AC:

714

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.054

DANN

Benign

0.059

DEOGEN2

Benign

0.0078

T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.00021

LIST_S2

Benign

0.29

.;T

MetaRNN

Benign

0.0038

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.060

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

0.89

N;N

REVEL

Benign

0.082

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.036

MVP

0.092

MPC

0.070

ClinPred

0.0033

GERP RS

-2.3

Varity_R

0.036

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over